The Laser Microbeam and Medical Program (LAMMP) is a NIH Biomedical Technology Resource Center dedicated to the use of lasers and optics in biology and medicine. LAMMP is located within the Beckman Laser Institute (BLI), an interdisciplinary biomedical research, teaching, and clinical facility at the University of California, Irvine. Overall resource objectives are to promote a well-balanced Center with activities in technological research and development, collaborative research, service, training, and dissemination. In this sixth renewal application of LAMMP, we continue to emphasize our unique capabilities to facilitate translational research by rapidly moving basic science and technology discoveries from blackboard to benchtop to bedside. This is accomplished by combining state of the art optical technologies with specialized resource facilities for cell and tissue engineering, histopathology, pre-clinical animal models, and clinical care. LAMMP provides both Microscopy and Microbeam Technologies (MMT) for high-resolution functional imaging and manipulation of living cells and tissues and Medical Translational Technologies (MTT) for non- and minimally-invasive monitoring, treating, and imaging pre-clinical animal models and human subjects. In addition, we propose to establish a new core, Virtual Photonics Technologies (VPT) for developing computational models and methods that advance the performance of biophotonic technologies, and enhance the information content derived from optical measurements. Seven Technology Research and Development projects are proposed that will result in the fabrication of several new instruments as well as the creation of multi-functional software. These projects build on our longstanding expertise in light-tissue interaction models and Biophotonics technologies, including laser microbeams, non-linear microscopy, optical coherence tomography, spatial/temporal modulation methods, and diffuse optics. LAMMP cores contain complementary technologies that are capable of quantitatively characterizing, imaging, and perturbing structure and biochemical function in cells and tissues with scalable resolution and depth sensitivity ranging from micrometers to centimeters. Collaborative studies are proposed that advance these technologies so they become widely-available, enabling methods in Biology and Medicine. Throughout the grant we emphasize the relevance of LAMMP technologies to Medicine in areas such as cancer, cardiovascular disease, metabolic syndrome, and neurologic function, as well as fundamental biological process, such as mechano-transduction, wound repair, angiogenesis, fibrosis, and cell death.